Abstract
We have recently characterized SCAI (Suppressor of Cancer Cell Invasion), a transcriptional modulator regulating cancer cell motility through suppression of MAL/SRF dependent gene transcription. We show here that SCAI is expressed in a wide range of normal human tissues and its expression is diminished in a large array of primary human breast cancer samples indicating that SCAI expression might be linked to the etiology of human cancer. To establish a functional link between SCAI and tumorigenesis we performed affinity columns to identify SCAI-interacting proteins. Our data show that SCAI interacts with the tumor suppressing SWI/SNF chromatin remodeling complex to promote changes in gene expression and the invasive capacities of human tumor cells. Moreover our data implicate a functional hierarchy between SCAI and BRM, since SCAI function is abrogated in the absence of BRM expression.
Highlights
Dynamic changes in chromatin architecture are necessary to adapt the transcriptional profile to specific changes of the physiological conditions
We show here that SCAI is functionally linked to SWI/ SNF complexes to promote changes in gene expression that may be critical for tumor cell invasion
We show that the expression of SCAI is restricted to the duct epithelia of the mammary gland, mainly expressed in the nucleus (Figure 1B)
Summary
Dynamic changes in chromatin architecture are necessary to adapt the transcriptional profile to specific changes of the physiological conditions. We show here that SCAI is functionally linked to SWI/ SNF complexes to promote changes in gene expression that may be critical for tumor cell invasion. MDA-MB-435 and MDA-MB-231 cells were transfected with specific siRNAs against BRM or SCAI for 48 h.
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